James Weisberger

Flow cytometry in the diagnosis of mediastinal tumors with emphasis on differentiating thymocytes from precursor T-lymphoblastic lymphoma/leukemia.

Flow cytometry (FC) has become the routine technique in the evaluation of hematopoietic neoplasms. Since the anterior mediastinum is a frequent site of involvement by both primary and secondary lymphoma/leukemia, flow cytometry plays an important role in the evaluation of mediastinal masses. The present study reviews 100 flow cytometry cases from patients presenting with mediastinal lesions. In 5 cases (5%) flow cytometry was not diagnostic due to either insufficient cell yield or low viability. In the remaining cases (95/100) cell suspensions were adequate for flow cytometry evaluation. Results showed that in 31/32 (96.8%), 2/3 (66.7%), 7/9 (77.8%), 7/8 (87.5%) and 11/11 (100%) cases of B-cell lymphoma, T-cell lymphoma, carcinoma, T-ALL/LBL and thymoma/thymic hyperplasia, respectively, the diagnosis could be reached by flow cytometry alone. Excluding HL, the general sensitivity of FC in diagnosing mediastinal tumors was ∼92%. Among the 100 cases, flow cytometry gave non-informative results in 3 cases of diffuse large B-cell lymphoma, 1 case of peripheral T-cell lymphoma, and 3 cases of carcinoma. No false positive results were encountered. The phenotypic pattern, especially surface CD3 expression versus forward scatter, reliably discriminated between immature thymocytes from thymoma/thymic hyperplasia from T-ALL/LBL. Flow methodology has the advantage of rapid turn-around time as well as high sensitivity, enabling patients with large anterior mediastinal masses and/or superior vena cava syndrome to begin treatment as promptly as possible. In experienced hands, flow cytometry plays a valuable and complementary role to histology and immunohistochemistry in diagnosing mediastinal tumors.

Colonic Adenomas with Extramedullary Myeloid Tumor (Granulocytic Sarcoma)

Extramedullary myeloid tumor (EMT) is an accumulation of malignant immature cells of the granulocytic series that is usually green in appearance due to the presence of myeloperoxidase. These invasive and destructive tumors occur most commonly in the skull and surrounding tissues, lymph nodes, skin and soft tissues. Regardless of the site, EMTs are difficult to recognize and may be easily overlooked or diagnosed as malignant lymphoma. EMTs may precede the diagnosis of a chronic myeloproliferative disorder or acute myeloid leukemia, may present coincident with the hematologic diagnosis, or may herald a relapse after therapy. An accurate diagnosis of EMT is of great clinical importance in the ongoing management of hematologic malignancies. We report here two unusual cases of EMT of the colon, which infiltrated adenomatous polyps. We conclude that increased cellularity within the lamina propria of polyps and mucosal surfaces in general should be carefully examined.

Differentiation of Extramedullary Acute Promyelocytic Leukemia by All-Trans-Retinoic Acid

The effect of all-trans-retinoic acid (ATRA) on extramedullary acute promyelocytic leukemia (APL) has not been fully delineated. We report an unusual case of APL in which a patient relapsed in the skin and central nervous system. Cytodifferentiation of leukemic cells from these extramedullary sites was demonstrated following treatment with ATRA.

Cytochemical diagnosis of Gaucher's disease by iron stain

Gaucher’s disease, the most common lysosomal storage disorder, arises from mutations in the gene encoding glucocerebrosidase. The glucocerebrosidase enzyme, which cleaves glucose from ceramide, is markedly reduced or absent. This results in accumulation of glucocerebroside, primarily in phagocytic cells. Of the various subtypes, the most common form, accounting for up to 99% of cases, is that of type I, or the chronic non-neuronopathic form. The disease is inherited in an autosomal recessive fashion, manifests in adulthood with splenic and skeletal involvement, and occurs predominantly in the Ashkenazi Jewish population. Clinical features include pathological fractures as well as cytopenia(s) caused by hypersplenism. The diagnosis is generally made by cytomorphologic examination of the bone marrow, and confirmed by measurement of glucocerebrosidase activity in peripheral blood leucocytes or cultured skin fibroblasts. Gaucher’s cells show diffuse and avid iron staining using a Prussian blue iron stain (left, Prussian blue stain with Wright–Giemsa inset), in contrast to normal bone marrow histiocytes or pseudo-Gaucher histiocytes associated with chronic myeloproliferative disorders such as chronic myeloid leukaemia (right, Prussian blue stain with Wright–Giemsa inset). This was determined over a generation ago to be probably due to phagocytosed erythrocytes. The current generation of haematologists and pathologists need to be aware of this phenomenon. Any histiocyte with diffuse iron uptake should be considered as highly suspicious for Gaucher’s disease, and an appropriate clinical work-up should be instituted.

Biphenotypic (mixed myeloid/T-cell) extramedullary myeloid cell tumor.

A 32-year-old male with a 4-year history of chronic myelogenous leukemia (CML) in chronic phase for 4 years, then myeloid blast crisis for 7 months, developed diffuse bulky lymphadenopathy in association with a white blood count (WBC) of 17,100/mm3 with 70% blasts. Biopsy of a cervical lymph node revealed a blastic extramedullary myeloid cell tumor, which showed a biphenotypic (mixed myeloid/T-cell) immunophenotype. Chromosomal analysis revealed karyotypic features of both myeloid and lymphoid lineages. Although extramedullary myeloid cell tumor (EMT, granulocytic sarcoma, chloroma) is well known to occur in chronic myelogenous leukemia (CML), to our knowledge this is the first description of evolution of CML into a biphenotypic EMT.

Failure of partial splenectomy to ameliorate the anemia of pyruvate kinase deficiency

The authors report a case of pyruvate kinase deficiency in a 4-year-old patient who required monthly blood transfusions. A partial splenectomy was performed to decrease the transfusion requirements and at the same time preserve splenic function. After removal of 80% of splenic tissue there was no amelioration of her transfusion needs. She responded well to subsequent total splenectomy performed 6 months later, and is currently well and transfusion independent. Rapid splenic regeneration possibly caused by erythrophagocytosis and extramedullary hematopoiesis is the presumed reason for this patients failure to respond to partial splenectomy.